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Acid-sensing pathways in rat gastrointestinal mucosa
Yasutada Akiba1, Masahiko Nakamura, Hiroshi Nagata
1Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Journal of Gastroenterology
|February 8, 2003
Summary
The gastrointestinal tract detects and defends against stomach acid using an "early warning" system. This involves the capsaicin pathway for blood flow and mucus, with the COX pathway regulating mucus secretion.
Area of Science:
- Gastroenterology
- Physiology
- Neurogastroenterology
Background:
- The gastrointestinal (GI) mucosa protects against luminal contents, including damaging gastric acid.
- Epithelial defense mechanisms are activated by an
Purpose of the Study:
- To investigate mechanisms defending the duodenal epithelium against luminal acid-induced injury.
- To elucidate pathways regulating epithelial intracellular pH (pHi), blood flow, and mucus secretion.
Main Methods:
- Perfused rat duodenum model to study responses to physiological acid concentrations.
- Investigated roles of Na+/H+ exchange, vanilloid receptors (VR), calcitonin gene-related peptide (CGRP), nitric oxide (NO) synthase, cyclooxygenase (COX), and sensory denervation.
Main Results:
- Luminal acid induced epithelial cell acidification, hyperemia, and increased mucus thickness.
- Hyperemic response was dependent on VR, CGRP, and NO pathways, but not COX.
- Mucus secretion was regulated by the capsaicin pathway (VR, CGRP, NO) and COX inhibition.
Conclusions:
- The capsaicin pathway acts as an acid-sensing system, promoting hyperemia and mucus secretion in the duodenum.
- The COX pathway serves as a secondary regulator for acid-induced mucus secretion.
- A similar acid-sensing pathway exists in the colon, indicating GI mucosa senses acidity via epithelial-VR communication.